| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Medicine, Pulmonary, Allergy, and Critical Care Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
Dendritic cells (DCs) sense various components of invading pathogens via pattern recognition receptors such as TLRs. CpG oligodeoxynucleotides (ODNs), which mimic bacterial DNA, inhibit allergic airways disease and promote responses in the spleen to bacterial components. Because many TLR agonists are currently being tested for potential therapeutic effects, it is important to characterize the expression and function of TLRs in different tissues. We show that both myeloid and plasmacytoid DCs in the spleen express TLR9, the receptor for CpG ODNs, but lung DCs show no detectable expression in either subset. TLR4 expression in contrast was detected on both lung and spleen DCs. LPS was superior to CpG ODN in increasing the allostimulatory potential of lung DCs and their expression of CD40. However, both agonists efficiently stimulated spleen DCs. CpG ODNs administered to mice efficiently inhibited Th2 cytokine production both in the lung draining lymph node and in the spleen. Surprisingly, inhibition of Th2 cytokine production was evident despite high levels of expression of GATA-3 and additional transcription factors that regulate Th2 responses. Although in the spleen CpG ODNs induced IL-6, a key cytokine induced via TLR9-MyD88 signaling, no IL-6 was detectable in lung LN cells. These studies show for the first time that lung DCs lack TLR9 expression, but, despite this deficiency, CpG ODNs induce potent inhibitory effects on Th2 cytokine production in the lung without inducing expression of the proinflammatory cytokine, IL-6, which has been linked to chronic diseases in the lung and the gut.
This article has been cited by other articles:
|
|
 |
|
  S. Takenaka, S. McCormick, E. Safroneeva, Z. Xing, and J. Gauldie Influence of the Tissue Microenvironment on Toll-Like Receptor Expression by CD11c+ Antigen-Presenting Cells Isolated from Mucosal Tissues Clin. Vaccine Immunol., November 1, 2009; 16(11): 1615 - 1623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Constabel, M. V. Stankov, C. Hartwig, T. Tschernig, and G. M. N. Behrens Impaired Lung Dendritic Cell Migration and T Cell Stimulation Induced by Immunostimulatory Oligonucleotides Contribute to Reduced Allergic Airway Inflammation J. Immunol., September 1, 2009; 183(5): 3443 - 3453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xu, T. B. Oriss, M. Fei, A. C. Henry, B. N. Melgert, L. Chen, A. L. Mellor, D. H. Munn, C. G. Irvin, P. Ray, et al. Indoleamine 2,3-dioxygenase in lung dendritic cells promotes Th2 responses and allergic inflammation PNAS, May 6, 2008; 105(18): 6690 - 6695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Zucchini, G. Bessou, S. H. Robbins, L. Chasson, A. Raper, P. R. Crocker, and M. Dalod Individual plasmacytoid dendritic cells are major contributors to the production of multiple innate cytokines in an organ-specific manner during viral infection Int. Immunol., January 1, 2008; 20(1): 45 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Guggemoos, D. Hangel, S. Hamm, A. Heit, S. Bauer, and H. Adler TLR9 Contributes to Antiviral Immunity during Gammaherpesvirus Infection J. Immunol., January 1, 2008; 180(1): 438 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Faith, E. Peek, J. McDonald, Z. Urry, D. F. Richards, C. Tan, G. Santis, and C. Hawrylowicz Plasmacytoid Dendritic Cells from Human Lung Cancer Draining Lymph Nodes Induce Tc1 Responses Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 360 - 367. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
